CASE OF THE WEEK
Editor: Mahmut Akgul (akgulm@amc.edu)
2022-09/February 28
Contributors: Chara Ntala, Marie O’Donell
A female in her 60s presented with a 2.4 cm solid and hypovascular left renal mass. She underwent diagnostic biopsy.
Quiz
1. What is the correct diagnosis?
a. Metanephric adenoma
b. Biphasic papillary renal cell carcinoma
c. Mucinous tubular and spindle cell carcinoma
d. MITF Translocation renal cell carcinoma
e. Fumarate hydratase deficient renal cell carcinoma
2. Which is the most common genetic alteration underlying this tumor?
a. BRAFV600E mutation
b. Succinate dehydrogenase B mutation
c. 7 and 17 chromosome gains
d. Xp11.2 translocation
1. b; 2. c
Biphasic papillary renal cell carcinoma
The core biopsy showed a tumour with an exclusively glomeruloid architectural growth pattern. These organoid areas were composed of clusters of larger cells with abundant eosinophilic cytoplasm and large vesicular nuclei that were surrounded by smaller bland basophilic cells. There were aggregates of macrophages present but no evidence of necrosis. A panel of immunohistochemistry was applied showing that the cells expressed PAX8, EMA, Vimentin, CK7 and AMACR. The cells were negative for CD57 and CD10. Only the larger cells within the biphasic areas expressed Cyclin D1. This morphology and immunophenotype supported the diagnosis of papillary renal cell carcinoma (RCC) with a biphasic growth pattern. The subsequent surgical excision showed an identical pattern of growth.
This is an emerging rare subtype of papillary RCC. It is worth noting that multiple descriptive terms have been employed to characterise this entity, including ‘biphasic alveolar’, ‘biphasic squamoid’ and ‘biphasic alveolar/squamoid’ and glomeruloid which can be confusing. The hallmark of this entity is the presence of two cell populations: clusters of larger squamoid cells and higher grade nuclei, surrounded by a second population of smaller cells with scant cytoplasm and low grade nuclei (resembling papillary RCC type 1) that form aggregates or nests resembling alveolar structures and glomeruli. The larger eosinophilic cells are designated as ‘squamoid’ due to their morphological resemblance to squamous cells but no definitive evidence of squamous differentiation is identified on light microscopy or with IHC (p63 or CK5/6). Both cell populations tend to be positive for PAX8, CK7, AMACR, EMA and variably for CD10. Cyclin D1 staining of the larger cells seems to be specific for this subtype. Some studies have also shown staining for CD57 in the large cells in a portion of cases. CAIX, CD117, GATA3, WT1, CK5/6 and CK20 all show negative staining.
The differential diagnosis, particularly in small biopsy samples, includes metanephric adenoma and mucinous tubular spindle cell carcinoma. Metanephric adenoma can show a papillary growth pattern but the biphasic morphology is absent. It has a distinct immunoprofile (WT1 +, CK7-, AMACR-), but CD57 staining of the large cells in a subpopulation of biphasic papillary RCC could potentially create confusion. Mucinous tubular and spindle cell carcinoma has identical immunoprofile but lacks the biphasic morphology; in contrast papillary RCC usually would lack spindle cell areas and mucinous stroma.
These tumours are reported to be commonly multifocal and associations with other kidney carcinomas have also been documented. Molecularly, it is characterised by gains of chromosomes 7 and 17. All these features further support this being part of the papillary RCC family. It is still unclear whether this pattern is significant although there have been some studies which have suggested that it might have a slightly more aggressive course compared with more typical papillary RCC. This remains to be confirmed in larger studies. Awareness of this entity is necessary for correct diagnosis in order to improve our understanding of the clinical behavior of renal tumors with papillary growth.
1. Trpkov K, Athanazio D, Magi-Galluzzi C, et al. Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases. Histopathology. 2018 Apr;72(5):777-785
2. Lobo J, Ohashi R, Helmchen BM, et al. The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth. Biomedicines. 2021 Oct 9;9(10):1418
3. Trpkov, Kiril, and Ondřej Hes. “New and Emerging Renal Entities: a Perspective post‐WHO 2016 Classification.” Histopathology 74.1 (2019): 31–59.
4. Petersson F, Bulimbasic S, Hes O, et al. Biphasic alveolosquamoid renal carcinoma: a histomorphological, immunohistochemical, molecular genetic, and ultrastructural study of a distinctive morphologic variant of renal cell carcinoma. Ann Diagn Pathol. 2012 Dec;16(6):459-69
5. Hes O, Condom Mundo E, Peckova K et al. Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma? Am J Surg Pathol. 2016 May;40(5):664-75
6. Lopez JI. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma. F1000Res. 2016 Apr 8;5:607
7.Troxell ML, Higgins JP. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma. Hum Pathol. 2016 Nov;57:28-36
8. Zhou L, Xu H, Zhou Y, et al. Biphasic squamoid alveolar renal carcinoma with positive CD57 expression: A clinicopathologic study of three cases. Pathol Int. 2019 Sep;69(9):519-525
Chara Ntala, Western General Hospital, Edinburgh, NHS Lothian, Scotland
Marie O’Donell, Western General Hospital, Edinburgh, NHS Lothian, Scotland
Kidney
Biphasic papillary carcinoma, papillary renal cell carcinoma, kidney, Cyclin D1